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Gastrointestinal cancer
Second-Line Fluoropyrimidine-Based Chemotherapy in Advanced Biliary Tract Cancer: A Meta-analysis Based on Individual Patient-Level Data of Randomized Trials
Jaewon Hyung, Minsu Kang, Ilhwan Kim, Kyu-pyo Kim, Baek-Yeol Ryoo, Jaekyung Cheon, Hyewon Ryu, Ji Sung Lee, Ji-Won Kim, In Sil Choi, Jin Hyun Park, Ghassan K. Abou-Alfa, Jin Won Kim, Changhoon Yoo
Cancer Res Treat. 2025;57(2):519-527.   Published online October 17, 2024
DOI: https://doi.org/10.4143/crt.2024.652
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head.
Materials and Methods
We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens.
Results
A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy.
Conclusion
Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

Citations

Citations to this article as recorded by  
  • Liposomal irinotecan for previously treated patients with biliary tract cancer: A pooled analysis of NIFTY and NALIRICC trials
    Changhoon Yoo, Anna Saborowski, Jaewon Hyung, Patrick Wenzel, Ilhwan Kim, Henning Wege, Kyu-pyo Kim, Gunnar Folprecht, Baek-Yeol Ryoo, Phillip Schütt, Jaekyung Cheon, Thorsten Götze, Hyewon Ryu, Ji Sung Lee, Arndt Vogel
    Journal of Hepatology.2025;[Epub]     CrossRef
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  • 114 Download
  • 1 Crossref
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Genitourinary cancer
Clinical Outcomes of Small Cell Carcinoma of the Genitourinary Tract and the Prognostic Significance of the Tumor Immune Microenvironment
Jaewon Hyung, Hyung-Don Kim, Gi Hwan Kim, Yong Mee Cho, Yeon-Mi Ryu, Sang-Yeob Kim, Inkeun Park, Shinkyo Yoon, Jae Lyun Lee
Cancer Res Treat. 2024;56(2):624-633.   Published online November 29, 2023
DOI: https://doi.org/10.4143/crt.2023.1076
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Small cell carcinoma of the genitourinary tract (GU SCC) is a rare disease with a poor prognosis. There are only limited treatment options due to insufficient understanding of the disease. In this study, we analyzed the clinical outcomes of patients with GU SCC and their association with the tumor immune phenotype.
Materials and Methods
Patients diagnosed with GU SCC were included. Survival outcomes according to the primary location (prostate and non-prostate) and stages (limited disease [LD] and extensive disease [ED]) were analyzed. We performed multiplex immunohistochemistry (IHC) in non-prostate SCC patients and analyzed the immune cell population.
Results
A total of 77 patients were included in this study. Their median age was 71 years, 67 patients (87.0%) were male, and 48 patients (62.3%) had non-prostate SCC. All patients with ED (n=31, 40.3%) received etoposide plus platinum (EP) as initial treatment and median overall survival (OS) was 9.7 months (95% confidence interval [CI], 7.1 to 18.6). Patients with LD (n=46, 59.7%) received EP followed by radiotherapy or surgery, and 24-months OS rate was 63.6% (95% CI, 49.9 to 81.0). The multiplex IHC analysis of 21 patients with non-prostate SCC showed that patients with a higher density of programmed death-ligand 1–expressing CD68+CD206+ M2-like macrophages had significantly worse OS outcomes with an adjusted hazards ratio of 4.17 (95% CI, 1.25 to 14.29; adjusted p=0.02).
Conclusion
Patients with GU SCC had a poor prognosis, even those with localized disease. The tumor immune phenotypes were significantly associated with survival. This finding provides new insights for treating GU SCC.
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Gastrointestinal cancer
GASTric Cancer HER2 Re-Assessment Study 2 (GASTHER2): HER2 Re-assessment for Initially HER2-Negative Advanced Gastric Cancer Patients after Progression on First-Line Treatment
Jaewon Hyung, Hyung-Don Kim, Min-Hee Ryu, Young Soo Park, Meesun Moon, Yoon-Koo Kang
Cancer Res Treat. 2024;56(1):199-207.   Published online June 20, 2023
DOI: https://doi.org/10.4143/crt.2023.490
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Heterogeneous human epidermal growth factor receptor 2 (HER2) overexpression in gastric cancer may lead to a misdiagnosis of HER2 status. Accurate assessment of HER2 status is essential for optimal treatment as novel HER2-directed agents are being investigated in various clinical settings. We evaluated the usefulness of HER2 re-assessment following progression on first-line treatment in initially HER2-negative advanced gastric cancer (AGC) patients.
Materials and Methods
We enrolled 177 patients with baseline HER2-negative AGC and performed HER2 re-assessment after progression on first-line treatment from February 2012 to June 2016 at Asan Medical Center, Seoul, Korea. The re-assessed HER2 status was analyzed with baseline HER2 status and clinical characteristics.
Results
The median age was 54 years (range, 24 to 80 years), and 123 patients (69.5%) were men. Seven patients (4.0%) were HER2-positive on the re-assessment. Patients with baseline HER2 negativity confirmed by a single test (n=100) had a higher HER2-positive re-assessment rate compared to those who had repeated baseline testing (n=77) (5.0% vs. 2.6%). Among the patients with single baseline HER2 testing, the rate was higher in patients with baseline HER2 immunohistochemistry (IHC) 1+ compared to those with IHC 0 (13.4% vs. 3.6%).
Conclusion
Overall, 4.0% of patients with baseline HER2-negative AGC were HER2-positive on re-assessment, and the HER2-positive re-assessment rate was higher among patients who had a single test at baseline. HER2 re assessment may be considered for initially HER2-negative patients to determine their eligibility for HER2-directed therapy, particularly if their HER2 negativity was determined by a single test, especially if they had a single baseline HER2 IHC 1+ test.

Citations

Citations to this article as recorded by  
  • Targeting HER2 in Gastroesophageal Cancer: A New Appetite for an Old Plight
    Antonella Cammarota, Rachel Woodford, Elizabeth C. Smyth
    Drugs.2025; 85(3): 361.     CrossRef
  • 3,706 View
  • 207 Download
  • 1 Web of Science
  • 1 Crossref
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Analysis of Plasma Circulating Tumor DNA in Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Modified FOLFIRINOX: Clinical Relevance of DNA Damage Repair Gene Alteration Detection
Dong-Hoon Lim, Hyunseok Yoon, Kyu-pyo Kim, Baek-Yeol Ryoo, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Song Cheol Kim, Seung-Mo Hong, Jaewon Hyung, Changhoon Yoo
Cancer Res Treat. 2023;55(4):1313-1320.   Published online May 4, 2023
DOI: https://doi.org/10.4143/crt.2023.452
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136).
Materials and Methods
Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival.
Results
Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations.
Conclusion
Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.

Citations

Citations to this article as recorded by  
  • A Review of Circulating Tumor DNA (ctDNA) in Pancreatic Cancer: Ready for the Clinic?
    Purvi Jonnalagadda, Virginia Arnold, Benjamin A. Weinberg
    Journal of Gastrointestinal Cancer.2025;[Epub]     CrossRef
  • A Practical Approach to Interpreting Circulating Tumor DNA in the Management of Gastrointestinal Cancers
    Zexi Allan, David S Liu, Margaret M Lee, Jeanne Tie, Nicholas J Clemons
    Clinical Chemistry.2024; 70(1): 49.     CrossRef
  • High somatic mutations in circulating tumor DNA predict response of metastatic pancreatic ductal adenocarcinoma to first-line nab-paclitaxel plus S-1: prospective study
    Lei Huang, Yao Lv, Shasha Guan, Huan Yan, Lu Han, Zhikuan Wang, Quanli Han, Guanghai Dai, Yan Shi
    Journal of Translational Medicine.2024;[Epub]     CrossRef
  • Decoding the Dynamics of Circulating Tumor DNA in Liquid Biopsies
    Khadija Turabi, Kelsey Klute, Prakash Radhakrishnan
    Cancers.2024; 16(13): 2432.     CrossRef
  • Building on the clinical applicability of ctDNA analysis in non-metastatic pancreatic ductal adenocarcinoma
    Ibone Labiano, Ana E. Huerta, Maria Alsina, Hugo Arasanz, Natalia Castro, Saioa Mendaza, Arturo Lecumberri, Iranzu Gonzalez-Borja, David Guerrero-Setas, Ana Patiño-Garcia, Gorka Alkorta-Aranburu, Irene Hernández-Garcia, Virginia Arrazubi, Elena Mata, Davi
    Scientific Reports.2024;[Epub]     CrossRef
  • Liquid biopsy analysis of lipometabolic exosomes in pancreatic cancer
    Wei Guo, Peiyao Ying, Ruiyang Ma, Zuoqian Jing, Gang Ma, Jin Long, Guichen Li, Zhe Liu
    Cytokine & Growth Factor Reviews.2023; 73: 69.     CrossRef
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Histopathologic and Molecular Biomarkers of PD-1/PD-L1 Inhibitor Treatment Response among Patients with Microsatellite Instability‒High Colon Cancer
Jaewon Hyung, Eun Jeong Cho, Jihun Kim, Jwa Hoon Kim, Jeong Eun Kim, Yong Sang Hong, Tae Won Kim, Chang Ohk Sung, Sun Young Kim
Cancer Res Treat. 2022;54(4):1175-1190.   Published online January 12, 2022
DOI: https://doi.org/10.4143/crt.2021.1133
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Recent clinical trials have reported response rates < 50% among patients treated with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors for microsatellite instability‒high (MSI-H) colorectal cancer (CRC), and factors predicting treatment response have not been fully identified. This study aimed to identify potential biomarkers of PD-1/PD-L1 inhibitor treatment response among patients with MSI-H CRC.
Materials and Methods
MSI-H CRC patients enrolled in three clinical trials of PD-1/PD-L1 blockade at Asan Medical Center (Seoul, Republic of Korea) were screened and classified into two groups according to treatment response. Their histopathologic features and expression of 730 immune-related genes from the NanoString platform were evaluated, and a machine learning–based classification model was built to predict treatment response among MSI-H CRCs patients.
Results
A total of 27 patients (15 responders, 12 non-responders) were included. A high degree of lymphocytic/neutrophilic infiltration and an expansile tumor border were associated with treatment response and prolonged progression-free survival (PFS), while mucinous/signet-ring cell carcinoma was associated with a lack of treatment response and short PFS. Gene expression profiles revealed that the interferon-γ response pathway was enriched in the responder group. Of the top eight differentially expressed immune-related genes, PRAME had the highest fold change in the responder group. Higher expression of PRAME was independently associated with better PFS along with histologic subtypes in the multivariate analysis. The classification model using these genes showed good performance for predicting treatment response.
Conclusion
We identified histologic and immune-related gene expression characteristics associated with treatment response in MSI-H CRC, which may contribute to optimal patient stratification.

Citations

Citations to this article as recorded by  
  • The Relationship of PRAME Expression with Clinicopathologic Parameters and Immunologic Markers in Melanomas: In Silico Analysis
    Yasemin Cakir, Banu Lebe
    Applied Immunohistochemistry & Molecular Morphology.2025; 33(2): 117.     CrossRef
  • Exploration of the regulatory mechanism of norcantharidin on sine oculis homeobox homolog 4 in colon cancer using transcriptome sequencing and bioinformatic
    Fanqin Zhang, Chao Wu, Jingyuan Zhang, Zhihong Huang, Antony Stalin, Yiyan Zhai, Shuqi Liu, Jiarui Wu
    Journal of Traditional Chinese Medical Sciences.2025;[Epub]     CrossRef
  • Biomarkers to predict efficacy of immune checkpoint inhibitors in colorectal cancer patients: a systematic review and meta-analysis
    Hang Yu, Qingquan Liu, Keting Wu, Shuang Tang
    Clinical and Experimental Medicine.2024;[Epub]     CrossRef
  • An Insight into the Peculiarities of Signet-Ring Cell Carcinoma of the Colon – a Narrative Review
    Loredana Farcaș, Diana Voskuil-Galoș
    Journal of Medical and Radiation Oncology.2024; 4(7): 1.     CrossRef
  • High serum IL-6 correlates with reduced clinical benefit of atezolizumab and bevacizumab in unresectable hepatocellular carcinoma
    Hannah Yang, Beodeul Kang, Yeonjung Ha, Sung Hwan Lee, Ilhwan Kim, Hyeyeong Kim, Won Suk Lee, Gwangil Kim, Sanghoon Jung, Sun Young Rha, Vincent E. Gaillard, Jaekyung Cheon, Chan Kim, Hong Jae Chon
    JHEP Reports.2023; 5(4): 100672.     CrossRef
  • Identification of ZBTB4 as an immunological biomarker that can inhibit the proliferation and invasion of pancreatic cancer
    Zhe Yang, Feiran Chen, Feng Wang, Xiubing Chen, Biaolin Zheng, Xiaomin Liao, Zhejun Deng, Xianxian Ruan, Jing Ning, Qing Li, Haixing Jiang, Shanyu Qin
    BMC Cancer.2023;[Epub]     CrossRef
  • PD-L1 Expression in Colorectal Carcinoma: A Comparison of 3 Scoring Methods in a Cohort of Jordanian Patients
    Heyam A. Awad, Maher A. Sughayer, Jumana M. Obeid, Yaqoot N. Heilat, Ahmad S. Alhesa, Reda M. Yousef, Nabil M. Hasasna, Shafiq A. Masoud, Tareq Saleh
    Applied Immunohistochemistry & Molecular Morphology.2023; 31(6): 379.     CrossRef
  • Systemic Delivery of a STING Agonist‐Loaded Positively Charged Liposome Selectively Targets Tumor Immune Microenvironment and Suppresses Tumor Angiogenesis
    Eun‐Jin Go, Hannah Yang, Wooram Park, Seung Joon Lee, Jun‐Hyeok Han, So Jung Kong, Won Suk Lee, Dong Keun Han, Hong Jae Chon, Chan Kim
    Small.2023;[Epub]     CrossRef
  • Review of the Immune Checkpoint Inhibitors in the Context of Cancer Treatment
    Norah A. Alturki
    Journal of Clinical Medicine.2023; 12(13): 4301.     CrossRef
  • Enhancing head and neck tumor management with artificial intelligence: Integration and perspectives
    Nian-Nian Zhong, Han-Qi Wang, Xin-Yue Huang, Zi-Zhan Li, Lei-Ming Cao, Fang-Yi Huo, Bing Liu, Lin-Lin Bu
    Seminars in Cancer Biology.2023; 95: 52.     CrossRef
  • Artificial intelligence for prediction of response to cancer immunotherapy
    Yuhan Yang, Yunuo Zhao, Xici Liu, Juan Huang
    Seminars in Cancer Biology.2022; 87: 137.     CrossRef
  • 6,799 View
  • 263 Download
  • 8 Web of Science
  • 11 Crossref
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Clinical Benefit of Maintenance Therapy for Advanced Biliary Tract Cancer Patients Showing No Progression after First-Line Gemcitabine Plus Cisplatin
Jaewon Hyung, Bumjun Kim, Changhoon Yoo, Kyo-pyo Kim, Jae Ho Jeong, Heung-Moon Chang, Baek-Yeol Ryoo
Cancer Res Treat. 2019;51(3):901-909.   Published online October 4, 2018
DOI: https://doi.org/10.4143/crt.2018.326
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Gemcitabine plus cisplatin (GemCis) is the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC). In ABC-02 study, the BTC patients received up to 6-8 cycles of 3-weekly GemCis; however, those without progression often receive more than 6-8 cycles. The clinical benefit of maintenance treatment in patients without progression is uncertain.
Materials and Methods
Advanced BTC patients treated with GemCis between April 2010 and February 2015 at Asan Medical Center, Seoul, Korea, were retrospectively analysed. The patients without progression after 6-8 cycles were stratified according to further treatment i.e., with or without further cycles of GemCis (maintenance vs. observation groups). The primary endpoint was overall survival (OS) and progression-free survival (PFS).
Results
Among the 740 BTC patients in the initial screen, 231 cases (31.2%) were eligible for analysis (111 in the observation group, 120 in the maintenance group). The median OS from the GemCis initiation was 20.5 months (95% confidence interval [CI], 15.4 to 25.6) and 22.4 months (95% CI, 17.0 to 27.8) in the observation and maintenance groups, respectively (p=0.162). The median PFS was 10.4 months (95% CI, 7.0 to 13.8) and 13.2 months (95% CI, 11.3 to 15.2), respectively (p=0.320).
Conclusions
GemCis maintenance is not associated with an improved survival outcome.

Citations

Citations to this article as recorded by  
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    Mascarenhas Chrystle, D'souza Sanyo
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  • Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer
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    Cancer Research and Treatment.2020; 52(3): 945.     CrossRef
  • Treatment of Metastatic or High-Risk Solid Cancer Patients by Targeting the Immune System and/or Tumor Burden: Six Cases Reports
    Andrea Nicolini, Paola Ferrari, Riccardo Morganti, Angelo Carpi
    International Journal of Molecular Sciences.2019; 20(23): 5986.     CrossRef
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